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Increased Levels of Heme‐Oxygenase‐1 Rescues Fructose‐Mediated Adipocyte Dysfunction
Author(s) -
Stevens Sarah,
Ansinelli Hayden,
Bellner Lars,
Khitan Zeid,
Abraham Nader
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.996.1
Subject(s) - apocynin , medicine , chemistry , endocrinology , adipocyte , uric acid , heme oxygenase , adipogenesis , lipid droplet , oxidative stress , fructose , reactive oxygen species , nadph oxidase , biochemistry , biology , heme , adipose tissue , enzyme
Obesity is an epidemic that is becoming increasingly more prevalent, particularly in Western societies, and is associated with an increase in oxidative stress. Unregulated fructose metabolism contributes to obesity by increasing reactive oxygen species (ROS). The aim of this study was to examine whether fructose and uric acid modulate adipogenesis in murine preadipocytes. We also hypothesize that an increase in HO‐1 will decrease ROS and adipocyte hypertrophy. Fructose (5 μM ‐ 1000 μM) and uric acid (10 mg/mL, ‐ 100 mg/mL) or apocynin (50‐500 mM) or allopurinol (550‐100 mM) were added to preadipocytes both in the presence and absence of cobalt protoporphyrin (CoPP), a known HO‐1 inducer. Fructose and uric acid decreased HO‐1 and Wnt10b expression and increased the expression of the adipogenic markers PPARγ, PEG‐1/Mest, and lipid accumulation. An increase in HO‐1 gene expression and HO activity decreased fructose and uric acid mediated lipid deposition and inflammatory cytokine levels, (IL‐1, IL‐6) and the expression of genes of the canonical Wnt signaling cascade (p<0.05). Preadipocytes treated with allopurinol and apocynin had a decreased number of large lipid droplets and ROS. These novel findings demonstrate that increased levels of HO‐1 appear crucial in modulating the phenotype of adipocytes exposed to both fructose and uric acid, in expressing canonical downstream signaling proteins, and in suppressing Peg‐1/Mest proteins, markers of adipocyte hyperplasia and inflammation. Furthermore, this data offers new insights into potential therapies by which targeting the production and/or downstream signaling of uric acid can curtail adipogenesis. Support NIH, HL‐55601, HL34300, BrickStreet Foundation (N.G.A.)